Methods for diagnosing irritable bowel syndrome

Abstract

The invention provides novel biomarkers, kits, and methods of diagnosing, prognosing, and subtyping IBS. Also provided are methods for aiding in the diagnosis of irritable bowel syndrome by detecting the serum level of novel IBS biomarkers identified herein.

1 . A method for aiding in the diagnosis of irritable bowel syndrome (IBS) in a subject, said method comprising:
 (a) contacting a blood or serum sample from the subject with an IBS marker binding moiety under conditions suitable to transform the IBS marker present in the sample into a complex comprising the IBS marker and the IBS marker binding moiety; and   (b) determining the level of said complex, thereby determining the level or concentration of the IBS marker present in the sample,   wherein the IBS marker is selected from the group consisting of carbohydrate deficient transferrin, urocortin, corticotrophin-releasing hormone-binding protein, cortisol, adrenocorticotropic hormone, substance P, nerve growth factor, neurokinin A, neurokinin B, vasoactive intestinal peptide, glucagon-like peptide 2, motilin, pituitary adenylate cyclase-activating peptide, serotonin, tryptophan, serotonin O-sulfate, 5-hydroxyindoleacetic acid, 5-HT glucuronide, tyrosine, phenylalanine, UDP-glucuronosyltransferase 1-6, serotonin reuptake transporter, tryptophan hydroxylase 1, monoamine oxidase A, monoamine oxidase B, and hydroxytryptamine (serotonin) receptor 3A.   
     
     
         2 . The method of  claim 1 , wherein the method further comprises:
 (c) comparing the level or concentration of the IBS marker present in the sample to a control level or concentration, wherein a difference in the level or concentration of the IBS marker present in the sample relative to the control level or concentration is indicative of an increased likelihood of said subject having IBS.   
     
     
         3 . The method of  claim 2 , wherein the control level or concentration is the level or concentration of the IBS marker present in a blood or serum sample from a healthy subject. 
     
     
         4 . The method of  claim 3 , wherein an increased level or concentration of the IBS marker present in the sample relative to the control level or concentration is indicative of an increased likelihood of said subject having IBS. 
     
     
         5 . The method of  claim 3 , wherein the same or a reduced level or concentration of the IBS marker present in the sample relative to the control level or concentration is indicative of an increased likelihood of said subject not having IBS. 
     
     
         6 . The method of  claim 2 , wherein the control level or concentration is the level or concentration of the IBS marker present in a blood or serum sample from a subject with IBS. 
     
     
         7 . The method of  claim 6 , wherein the same or an increased level or concentration of the IBS marker present in the sample relative to the control level or concentration is indicative of an increased likelihood of said subject having IBS. 
     
     
         8 . The method of  claim 6 , wherein a reduced level or concentration of the IBS marker present in the sample relative to the control level or concentration is indicative of an increased likelihood of said subject not having IBS. 
     
     
         9 - 38 . (canceled) 
     
     
         39 . The method of  claim 1 , wherein the method further comprises determining the level or concentration of at least one additional biomarker in a biological sample from the subject, the biomarker selected from the group consisting of Brain-Derived Neurotropic Factor (BDNF), Neutrophil Gelatinase-Associated Lipocalin (NGAL), TNF-related Weak Inducer of Apoptosis (TWEAK), Growth-Related Oncogene Alpha (GRO-α), Interleukin-1 Beta (IL-1β), Tissue Inhibitor of Metalloproteinase-1 (TIMP-1), Anti- Saccharomyces cerevisiae  Antibody (ASCA-IgA), Anti-CBir-1 Antibody (CBir1), Anti-Human Neutrophil Cytoplasmic Antibody (ANCA), Anti-Human Tissue Transglutaminase IgA (tTG), histamine, β-tryptase, prostaglandin E 2  (PGE 2 ), and a combination thereof. 
     
     
         40 . The method of  claim 1 , wherein the method further comprises:
 (d) determining a symptom profile for the subject, wherein said symptom profile is determined by identifying the presence or severity of at least one symptom in said subject; and   (e) diagnosing the subject as having IBS or not having IBS using an algorithm based upon the level of an IBS biomarker and the symptom profile.   
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . The method of  claim 1  wherein the method comprises the use of an algorithm based upon the level of an IBS biomarker. 
     
     
         44 - 50 . (canceled) 
     
     
         51 . A method for monitoring the progression or regression of irritable bowel syndrome (IBS) in a subject, the method comprising:
 (a) contacting a first blood or serum sample taken from the subject at a first time with an IBS marker binding moiety under conditions suitable to transform the IBS marker present in the sample into a complex comprising the IBS marker and the IBS marker binding moiety;   (b) determining the level of said complex, thereby determining the level of the IBS marker present in the first sample;   (c) contacting a second blood or serum sample taken from the subject at a second time with the IBS marker binding moiety under conditions suitable to transform the IBS marker present in the sample into a complex comprising the IBS marker and the IBS marker binding moiety;   (d) determining the level of said complex, thereby determining the level of the IBS marker present in the second sample; and   (e) comparing the level of the IBS marker present in the first sample to the level of the IBS marker present in the second sample,   wherein a higher level of the IBS marker in the second sample relative to the first sample is indicative of the progression of IBS in the subject and a lower level of the IBS marker in the second sample relative to the first sample is indicative of the regression of IBS in the subject, and   wherein the IBS marker is selected from the group consisting of carbohydrate deficient transferrin, urocortin, corticotrophin-releasing hormone-binding protein, cortisol, adrenocorticotropic hormone, substance P, nerve growth factor, neurokinin A, neurokinin B, vasoactive intestinal peptide, glucagon-like peptide 2, motilin, pituitary adenylate cyclase-activating peptide, serotonin, tryptophan, serotonin O-sulfate, 5-hydroxyindoleacetic acid, 5-HT glucuronide, tyrosine, phenylalanine, UDP-glucuronosyltransferase 1-6, serotonin reuptake transporter, tryptophan hydroxylase 1, monoamine oxidase A, monoamine oxidase B, and hydroxytryptamine (serotonin) receptor 3A.   
     
     
         52 - 80 . (canceled) 
     
     
         81 . The method of  claim 51 , wherein the method further comprises determining the level of at least one additional biomarker in a biological sample from the subject, the biomarker selected from the group consisting of Brain-Derived Neurotropic Factor (BDNF), Neutrophil Gelatinase-Associated Lipocalin (NGAL), TNF-related Weak Inducer of Apoptosis (TWEAK), Growth-Related Oncogene Alpha (GRO-α), Interleukin-1 Beta (IL-1β), Tissue Inhibitor of Metalloproteinase-1 (TIMP-1), Anti- Saccharomyces cerevisiae  Antibody (ASCA-IgA), Anti-CBir-1 Antibody (CBir1), Anti-Human Neutrophil Cytoplasmic Antibody (ANCA), Anti-Human Tissue Transglutaminase IgA (tTG), histamine, β-tryptase, prostaglandin E 2  (PGE 2 ), and a combination thereof. 
     
     
         82 . The method of  claim 51 , wherein the method further comprises determining a symptom profile for the subject, wherein said symptom profile is determined by identifying the presence or severity of at least one symptom in said subject. 
     
     
         83 . (canceled) 
     
     
         84 . The method of  claim 51 , wherein the method comprises the use of an algorithm based upon the level of an IBS biomarker. 
     
     
         85 - 90 . (canceled) 
     
     
         91 . A computer-readable medium comprising code for controlling one or more processors to classify whether a serum or blood sample from an subject is associated with irritable bowel syndrome (IBS), said code comprising:
 instructions to apply a statistical process to a data set comprising a diagnostic marker profile to produce a statistically derived decision classifying said sample as an IBS sample or non-IBS sample based upon said diagnostic marker profile,   wherein said diagnostic marker profile indicates the level of at least one diagnostic IBS marker selected from the group consisting of carbohydrate deficient transferrin, urocortin, corticotrophin-releasing hormone-binding protein, cortisol, adrenocorticotropic hormone, substance P, nerve growth factor, neurokinin A, neurokinin B, vasoactive intestinal peptide, glucagon-like peptide 2, motilin, pituitary adenylate cyclase-activating peptide, serotonin, tryptophan, serotonin O-sulfate, 5-hydroxyindoleacetic acid, 5-HT glucuronide, tyrosine, phenylalanine, UDP-glucuronosyltransferase 1-6, serotonin reuptake transporter, tryptophan hydroxylase 1, monoamine oxidase A, monoamine oxidase B, and hydroxytryptamine (serotonin) receptor 3A.   
     
     
         92 - 117 . (canceled) 
     
     
         118 . The computer-readable medium of  claim 91 , wherein the diagnostic marker profile indicates the level of at least one additional diagnostic marker in a biological sample from the subject selected from the group consisting of Brain-Derived Neurotropic Factor (BDNF), Neutrophil Gelatinase-Associated Lipocalin (NGAL), TNF-related Weak Inducer of Apoptosis (TWEAK), Growth-Related Oncogene Alpha (GRO-α), Interleukin-1 Beta (IL-β), Tissue Inhibitor of Metalloproteinase-1 (TIMP-1), Anti- Saccharomyces cerevisiae  Antibody (ASCA-IgA), Anti-CBir-1 Antibody (CBir1), Anti-Human Neutrophil Cytoplasmic Antibody (ANCA), Anti-Human Tissue Transglutaminase IgA (tTG), histamine, β-tryptase, prostaglandin E 2  (PGE 2 ), and a combination thereof. 
     
     
         119 . The computer-readable medium of  claim 91 , wherein said computer-readable medium comprises instructions to apply a statistical process to a data set comprising said diagnostic marker profile in combination with a symptom profile which indicates the presence or severity of at least one symptom in said subject to produce a statistically derived decision classifying said sample as an IBS sample or non-IBS sample based upon said diagnostic marker profile and said symptom profile. 
     
     
         120 - 122 . (canceled) 
     
     
         123 . A system for classifying whether a serum or blood sample from a subject is associated with irritable bowel syndrome (IBS), said system comprising:
 (a) a data acquisition module configured to produce a data set comprising a diagnostic marker profile, wherein said diagnostic marker profile indicates the presence or level of at least one diagnostic IBS marker selected from the group consisting of carbohydrate deficient transferrin, urocortin, corticotrophin-releasing hormone-binding protein, cortisol, adrenocorticotropic hormone, substance P, nerve growth factor, neurokinin A, neurokinin B, vasoactive intestinal peptide, glucagon-like peptide 2, motilin, pituitary adenylate cyclase-activating peptide, serotonin, tryptophan, serotonin O-sulfate, 5-hydroxyindoleacetic acid, 5-HT glucuronide, tyrosine, phenylalanine, UDP-glucuronosyltransferase 1-6, serotonin reuptake transporter, tryptophan hydroxylase 1, monoamine oxidase A, monoamine oxidase B, and hydroxytryptamine (serotonin) receptor 3A;   (b) a data processing module configured to process the data set by applying a statistical process to the data set to produce a statistically derived decision classifying said sample as an IBS sample or non-IBS sample based upon said diagnostic marker profile; and   (c) a display module configured to display the statistically derived decision.   
     
     
         124 - 149 . (canceled) 
     
     
         150 . The system of  claim 123 , wherein the diagnostic marker profile indicates the level of at least one additional diagnostic marker in a biological sample from the subject selected from the group consisting of Brain-Derived Neurotropic Factor (BDNF), Neutrophil Gelatinase-Associated Lipocalin (NGAL), TNF-related Weak Inducer of Apoptosis (TWEAK), Growth-Related Oncogene Alpha (GRO-α), Interleukin-1 Beta (IL-β), Tissue Inhibitor of Metalloproteinase-1 (TIMP-1), Anti- Saccharomyces cerevisiae  Antibody (ASCA-IgA), Anti-CBir-1 Antibody (CBir1), Anti-Human Neutrophil Cytoplasmic Antibody (ANCA), Anti-Human Tissue Transglutaminase IgA (tTG), histamine, β-tryptase, prostaglandin E2 (PGE2), and a combination thereof. 
     
     
         151 . The system of  claim 123 , wherein said data processing module comprises instructions to apply a statistical process to a data set comprising said diagnostic marker profile in combination with a symptom profile which indicates the presence or severity of at least one symptom in said subject to produce a statistically derived decision classifying said sample as an IBS sample or non-IBS sample based upon said diagnostic marker profile and said symptom profile. 
     
     
         152 - 154 . (canceled)